Assisted Reproduction Center, Clinical Center, University of Debrecen, Debrecen, Hungary.
Department of Obstetrics and Gynecology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Gynecol Obstet Invest. 2024;89(2):150-158. doi: 10.1159/000537836. Epub 2024 Feb 17.
The objective of this study was to analyze the impact of thyroid autoimmunity (TAI) on reproductive outcome parameters of intracytoplasmic sperm injection (ICSI) cycles as compared to TAI-negative ICSI cycles.
In this single in vitro fertilization (IVF) center retrospective study, 86 infertile women with elevated thyroid peroxidase or TGAb levels, but euthyroid after thyroxine replacement (study group), were compared to 69 female patients with no thyroid abnormalities (controls). Following ICSI treatment fertilization rate (FR), clinical pregnancy rate (CPR), miscarriage rate (MR), and live birth rate (LBR) were analyzed.
MATERIALS, SETTING, METHODS: All subjects with various infertility factors were treated with ICSI in university-based IVF center. Patients in the study group received thyroxine replacement and were euthyroid at IVF treatment. Before the IVF cycles, endocrinological parameters were uniformly assessed: thyroid function and antibodies, reproductive hormones (anti-Müllerian hormone [AMH], follicular stimulating hormone [FSH], luteinizing hormone, E2, PRL, testosterone, DHEAS, 17-OHP, AD) and OGTT (0-60-120 min glucose and insulin). Following descriptive comparison of laboratory parameters, age-adjusted analyses of FR, CPR, MR, and LBR were performed.
TAI-positive women were older (mean age 35.31 ± 4.95 vs. 32.15 ± 4.87 years; p = 0.002), had higher FSH (8.4 ± 3.4 vs. 7.4 ± 2.32 U/L; p = 0.024), higher E2 (53.94 ± 47.61 vs. 42.93 ± 18.92 pg/mL; p = 0.025) levels, while AMH (2.88 ± 2.62 vs. 3.61 ± 1.69 ng/mL; p = 0.0002) was lower. There were no differences in TSH levels (1.64 ± 0.96 vs. 1.66 ± 0.65 µIU/mL; p = 0.652) between the two groups. FT3 (2.63 ± 0.58 vs. 2.98 ± 0.55 pg/mL; p = 0.002) was lower and FT4 (1.3 ± 0.29 vs. 1.13 ± 0.21 ng/dL; p = 0.0002) was higher in the TAI-positive group, reflecting clinically irrelevant differences. Egg cell counts (6 ± 3.8 vs. 7.5 ± 3.95; p = 0.015) were lower in TAI and remained so following age adjustment. Although the overall ICSI FR did not differ (62.9% vs. 69.1%, p = 0.12), it was lower for patients under 35 with TAI showing decreasing differences in line with age. The CPR (36.04% vs. 69.56%; p < 0.001) and LBR (23.25% vs. 60.86%; p < 0.001) were lower, the MR (35.48% vs. 12.5%; p = 0.024) was higher in the TAI group, and these differences remained after age adjustment.
Since the higher age of the study group may interfere with the effect of TAI, age adjustment calculations were necessary to perform to eliminate this confounding factor.
Despite optimal thyroid supplementation in clinical or subclinical hypothyroidism, the presence of TAI negatively influences CPR and is connected to a higher MR, thus resulting in a lower LBR after ICSI. Decreased FR with ICSI in TAI patients may also contribute to poorer outcomes, especially in younger women.
本研究旨在分析甲状腺自身免疫(TAI)对卵胞浆内单精子注射(ICSI)周期生殖结局参数的影响,并与 TAI 阴性 ICSI 周期进行比较。
在这项单中心体外受精(IVF)回顾性研究中,将 86 名甲状腺过氧化物酶或 TGAb 水平升高但甲状腺素替代治疗后甲状腺功能正常的不孕妇女(研究组)与 69 名无甲状腺异常的女性患者(对照组)进行比较。分析 ICSI 治疗后的受精率(FR)、临床妊娠率(CPR)、流产率(MR)和活产率(LBR)。
材料、地点、方法:所有具有不同不孕因素的患者均在大学 IVF 中心接受 ICSI 治疗。研究组患者接受甲状腺素替代治疗,IVF 治疗时甲状腺功能正常。在 IVF 周期前,统一评估内分泌参数:甲状腺功能和抗体、生殖激素(抗苗勒管激素[AMH]、卵泡刺激素[FSH]、黄体生成素、E2、PRL、睾酮、DHEAS、17-羟孕酮、AD)和 OGTT(0-60-120 分钟血糖和胰岛素)。在比较实验室参数的描述性后,进行 FR、CPR、MR 和 LBR 的年龄调整分析。
TAI 阳性妇女年龄较大(平均年龄 35.31 ± 4.95 岁 vs. 32.15 ± 4.87 岁;p = 0.002),FSH 较高(8.4 ± 3.4 岁 vs. 7.4 ± 2.32 U/L;p = 0.024),E2 水平较高(53.94 ± 47.61 岁 vs. 42.93 ± 18.92 pg/mL;p = 0.025),而 AMH 较低(2.88 ± 2.62 岁 vs. 3.61 ± 1.69 ng/mL;p = 0.0002)。两组间 TSH 水平无差异(1.64 ± 0.96 岁 vs. 1.66 ± 0.65 µIU/mL;p = 0.652)。FT3(2.63 ± 0.58 岁 vs. 2.98 ± 0.55 pg/mL;p = 0.002)较低,FT4(1.3 ± 0.29 岁 vs. 1.13 ± 0.21 ng/dL;p = 0.0002)较高,反映出临床无意义的差异。TAI 阳性组的卵子计数(6 ± 3.8 岁 vs. 7.5 ± 3.95 岁;p = 0.015)较低,调整年龄后仍如此。尽管总体 ICSI FR 无差异(62.9% vs. 69.1%,p = 0.12),但 TAI 患者中年龄小于 35 岁的患者 FR 较低,且随着年龄的增长,这种差异呈下降趋势。CPR(36.04% vs. 69.56%;p < 0.001)和 LBR(23.25% vs. 60.86%;p < 0.001)较低,MR(35.48% vs. 12.5%;p = 0.024)较高,调整年龄后这些差异仍然存在。
由于研究组年龄较高可能会干扰 TAI 的影响,因此需要进行年龄调整计算以消除这种混杂因素。
尽管在亚临床甲状腺功能减退症患者中进行了最佳的甲状腺素替代治疗,但 TAI 的存在仍会对 CPR 产生负面影响,并与较高的 MR 相关,从而导致 ICSI 后 LBR 降低。TAI 患者的 ICSI FR 降低也可能导致妊娠结局较差,尤其是在年轻女性中。